文章基本信息

标题：LINGO1 is a regulatory subunit of large conductance, Ca2+-activated potassium channels
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作者：Srikanth Dudem ; Roddy J. Large ; Shruti Kulkarni 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：4
页码：2194-2200
DOI：10.1073/pnas.1916715117
出版社：The National Academy of Sciences of the United States of America
摘要：LINGO1 is a transmembrane protein that is up-regulated in the cerebellum of patients with Parkinson’s disease (PD) and Essential Tremor (ET). Patients with additional copies of the LINGO1 gene also present with tremor. Pharmacological or genetic ablation of large conductance Ca²⁺-activated K⁺ (BK) channels also result in tremor and motor disorders. We hypothesized that LINGO1 is a regulatory BK channel subunit. We show that 1) LINGO1 coimmunoprecipitated with BK channels in human brain, 2) coexpression of LINGO1 and BK channels resulted in rapidly inactivating BK currents, and 3) LINGO1 reduced the membrane surface expression of BK channels. These results suggest that LINGO1 is a regulator of BK channels, which causes a “functional knockdown” of these currents and may contribute to the tremor associated with increased LINGO1 levels.
关键词：BK channels ; leucine-rich repeat containing proteins ; LINGO1 ; accessory subunits ; Parkinson’s disease